Novel, medically useful antiparasitic compounds known as korupensamines have recently been described (Hallock et al., J. Org. Chem., 59, 6349-6355, 1994; Bringmann et al., Heterocycles, 39, 503-512, 1994; Boyd et al., U.S. Pat. No. 5,409,938). Korupensamines are members of a general chemical class of compounds known as monomeric naphthylisoquinoline alkaloids (Bringmann, The Alkaloids, Vol. 29 (Brossi, ed.), Academic Press, New York, 1986, pp. 141-184) which are characterized in part by their possession of a C-8' to C-5 naphthalene/isoquinoline linkage.
A method of chemically synthesizing korupensamines and related C-8' to C-5 linked naphthylisoquinoline alkaloids has heretofore been unknown. This is significant because the only known natural source of any korupensamine is the rare tropical vine Ancistrocladus korupensis of Central Africa (Thomas and Gereau, Novon, 3, 494-498, 1993; Hallock et al., 1994, supra). This lack of any synthetic access to korupensamines undoubtedly has been a critical hindrance to the medical use of the compounds, and to the exploration of alternative medical uses as well.
In addition to the korupensamines, a series of other medically useful monomeric naphthylisoquinoline alkaloids and derivatives thereof has been described (Francois et al., Phytochemistry, 35, 1461-1464, 1994; Francois et al., U.S. patent application Ser. No. 08/195,547). Similar to the korupensamines, these "non-korupensamine" monomeric naphthylisoquinoline alkaloids have been in exceedingly limited supply since they also are obtained from scarce plants having a limited geographic distribution. These other monomeric naphthylisoquinoline alkaloids differ from the korupensamines in their lack of a C-8' to C-5 naphthalene/isoquinoline linkage.
Accordingly, it is an object of the present invention to provide methods of chemically synthesizing known and new monomeric naphthylisoquinoline alkaloids, including korupensamines, derivatives thereof, and other monomeric naphthylisoquinolines (i.e., those lacking a C-8' to C-5 naphthalene/isoquinoline linkage).
Correspondingly, it is another object of the present invention to provide new monomeric naphthylisoquinoline compounds. Such compounds have particular use as therapeutic agents, for instance, as antiparasitic agents, and/or may serve as precursors or building blocks for the synthesis of dimeric naphthylisoquinoline compounds, such as exemplified by the michellamines (Bringmann et al., Tetrahedron, 50, 9643-9648, 1994; concurrently filed Bringmann et al., U.S. patent application; Boyd et al., J. Med. Chem., 37, 1740-1745, 1994), which have proven to be medically useful.
These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.